Paper having areas dissolvable in water

ABSTRACT

A method and article are provided with the method comprising instructing individuals in the effectiveness of bactericidal compositions by the steps of demonstrating to the individuals a graphic representation of micro-organisms upon paper or film which when immersed in water will result in the destruction of any graphic representation upon the surface of the paper or film, and immersing the paper or film in water. The preferred substrate is water-soluble paper prepared for example from cellulose ether fibers which ethers are soluble in cold water, all as is more particularly described in the following specification.

United States Patent lnventor Roland Henry Noel Fayetteville, N.Y.

Appl. No, 736,828

Filed June 13, 1968 Patented July 27, 1971 Assignee Bristol-Myers Company New York, N.Y.

PAPER HAVING AREAS DISSOLVABLE lN WATER 3 Claims, 1 Drawing Fig.

US. Cl 35/50,

Int. Cl G09b 23/28 Field of Search 283/5, 6;

[56] References Cited UNITED STATES PATENTS 2,402,542 6/1946 Foote ll7/l 3,034,922 5/l962 Boe 117/63 Primary ExaminerHarland S. Skogquist Atrorneysl-lerbert W, Taylor, Jr. and Richard H. Brink H. influenzue D. pneumoniue Betu-hemolyti c streptococci Sensitive stcphylococcl Salmonellae Enlerococci P. mircbilis Gonococci PAPER HAVING AREAS DISSOLVABLE IN WATER This invention relates to a method of demonstrating the effectiveness of antibiotic or bactericidal compositions.-

One of the foremost problems in the continuing education of physicians and others involved in the medical profession is to keep such individuals informed of the effectiveness and mode of action of known and existing antibiotics and other hactericides, as well as the lack of effectiveness thereof, against a wide variety of specific micro-organisms. The time required to keep abreast of the literature is beyond the limits of that available to the average physician, and standard reference works relied upon are not strictly current with newer developments. Bactericides of course vary widely in their effectiveness against specific organisms, some being more effective against a given organism than others. Also, in the case of broad spectrum antibiotics, they vary in side effects as well as in the breadth of effectiveness. At times, materials which are highly effective against a wide variety of organisms are prescribed even though there may be other materials, of equaleffectiveness against the specific organisms involved, which involve fewer possible side effects. The need is thus apparent for a simple, fast, means of educating those in the medical profession as to the effectiveness of bactericidal compounds and compositions and their mode of action and such means for teaching these facts must be not only rapid, but such as to impress upon the mind of the individual concerned the basic facts involved in such a way that they will be retained in this memory.

This invention provides such a means and method of educating individuals in the effectiveness and mode of action of such compounds and compositions.

The drawing illustrates the preferred embodiment of the invention. The illustrated embodiment includes a strip of paper or film l which is soluble in water, or at least the surface of which disintegrates when the strip is placed in water, carrying thereupon physical likenesses 2 of a wide variety of Grampositive and Gram-negative organisms. The specific bactericidal agent involved, effective against the given organisms, is a composition sold under the trade name of Polycilli'n, a synthetic penicillin (ampicillin trihydrate) with an extended spectrum against Gram-positive organisms and against certain Gram-negative pathogens. Among the Gram-positive organisms against which the material is effective are hemolytic and nonhemolytic streptococci, D. pneumoniae, nonpenicillinaseproducing Staphylococci, Clostridia spp., B. anlhracis, C. xerosis, and most strains of Enterococci. Among the Gramnegative organisms against which the composition is effective are H. influenzae, B.fundulifrmis, N. gonorrhueae, N. meningilidix, Br. abortus, Br, melirensis, Proteus mirabilis, and many strains of Salmonella, Shigella, and Escherichia. Not illustrated is a further embodiment of the invention comprising a section of the paper or film containing representations of an organism, or organisms against which the bactericidal agent is not effective, such as penicillinase-producing staphylococci.

In use, the strip with the graphic representation of the micro-organisms thereupon is caused to be demonstrated to the student for a period of time sufficient for him to digest the identity of the organisms represented, and it is then immersed in water, for example in a test tube. The dissolution of the paper or the disappearance of the graphic representations of the organisms impresses upon the student the effectiveness and mode of action of the antibiotic. in the case where the image on a portion of the strip is not destroyed because of the nature of the paper and printing utilized, the face is also im-- pressed upon the student as to contraindications which are present; i.e., organisms against which the particular antimicrobial agent is not effective.

The preferred type of paper or film utilized is prepared from cold water soluble cellulose ethers, particularly those which may be formed into fibers and which are insoluble in organic solvents or hot water. Of course, utilizing proper methods of manufacture, the substituted cellulose may be prepared in fiber form and used in this form to prepare paper. It is important that the cellulose ether have the proper degree of substitution (DS) in order to be cold water soluble. Thus, if too few of the three available hydroxyl groups on each anhydroglucose unit are substituted with methyl groups, for example (as in the case where the average degree of substitution for methyl cellulose is less than about 0.6) the produce is soluble in water only which has been made alkaline, with a material such as sodium hydroxide. If the degree of substitution is above about 2.6, for methylcellulose, the product is insoluble in cold water although soluble in alcohol, organic solvents, and hydrocarbons. Similarly, ethyl cellulose having a degree of substitution less than about 0.8 or greater than about 1.3 is unsuitable. In other words, methyl cellulose having a degree of substitution from about 1.3 to 2.6 is preferred as is ethyl cellulose having a degree of substitution from about 0.8 to about 1.3. It is to be understood that similar considerations are applicable to other cellulose derivatives. It is not essential that the water-soluble cellulose derivative be insoluble in hot water, although this is preferred. Useful products insoluble in hot water which are soluble in cold water include ethylhydroxyethyl cellulose (manufactured in Sweden and sold under the trade name of Modocoll and having an ethyl D5 of 0.7 to 1.3 and a hydroxyethyl DS of 0.9 to 0.5), hydroxyethylmethyl cellulose (made in Germany and sold under the trademark of Viscontran, having a viscosity, ofa 2 percent aqueous solution at 20 C. (Hoppler) of from about 300 to about 4,000, and Tylose having a viscosity, of a 2 percent aqueous solu tion at 20 C. (Ubbelohde) of from about 25 to about 15,000], methylethyl cellulose having a degree of substitution of methyl groups of 0.4 and of ethyl groups of 0.9 (sold under the trademarks Cellofas and Edifas in Great Britian) and methylhydroxypropyl cellulose and methyl cellulose, the preferred materials, both made in the United States (sold under the trademark Methocel). Among the useful materials which are soluble in both hot and cold water are sodium carboxymethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose and sodium cellulose sulfate.

Other water-soluble materials such as sodium alginate, hydrolyzed polyvinyl chloride, and polyvinyl alcohol fibers or films may be utilized, although the cellulose ethers described above are preferred since they react toward atmospheric humidity in a like manner to paper made of cellulose fibers. That is, the moisture content of the cold-water-soluble cellulose ether papers varies with the relative humidity in the air.

The paper may be manufactured by ordinary papermaking methods for forming waterlaid paper, but using hot water or a liquid in which the fibers are insoluble as the suspending medium for the fibers, all as more particularly disclosed in U.S. Pat. No. 2,648,635 incorporated herein by reference. Other destructible papers which, upon immersion in water, result in the destruction of an image appearing upon the surface thereof, are useful. For example, papers which expand rapidly in water or which have a water-soluble surface coating such as are disclosed in U.S. Pat. Nos. 2,402,542; 2,893,754; and 3,034,922 are within the invention.

EXAMPLE Methyl cellulose fibers having a degree of substitution of about 1.8 are dispersed in hot water and treated in a beater with a 2 percent solution of Igepon CN-42," sodium N- cyclohexyl-N-palmitoyl taurate, a low-foaming detergent, the temperature of the water being about F. and containing 0.5 percent by weight of the methyl cellulose fibers. This slurry is then waterlaid using a screen having a vacuum device on the underside thereof to form paper slightly thinner than ordinary writing paper. immediately after the water is drawn through the resulting web, it is subjected to drying using elevated temperatures above the gelling temperature of the methyl cellulose. The paper is then imprinted with the graphic representations shown in the drawing.

The student is shown or examines the teaching article or device, after which it is placed in a test tube ofcold water. The paper and the image simply dissolve, impressing upon the student the effectiveness of the antibiotic and the mode of action for combating particular micro-organisms.

In place of the wetting agent utilized in the example, other synthetic detergents may be utilized, examples of which may be found in the Oct. 22, 1955 edition of Chemical Week, pages 46-82. Also, the water in which the device is immersed may contain a wetting agent.

The gelling temperature referred to above is the tcmperw ture at which the cellulose ether precipitates from a cold solution of the same when it is heated. In the event water is the dispersing medium for the slurry used in forming the web, the temperature of the aqueous suspension of fibers must be above the gelling temperature. Although the drawing of the above example relates to demonstrating effectiveness of Polycillin, other antibiotics and bacterial agents such as Krantrex," Prostaphlin," Staphcillin," Syncillin," legopen,Dynapen," and others may as well be the subject of the educational method and article of the invention.

In addition to the methods disclosed above for forming the sheet or paper, a felt may be airlaid or mechanically deposited without the use of water, and, as suggested above, continuous films of the water soluble material may be utilized in lieu of paper.

lclaim:

1. An instructional paper for demonstrating the effectiveness of a microbiocidal composition comprising a paper sheet having a plurality of first and second spaced isolated areas, the first of said isolated areas being composed of a cold-watersoluble material, each of these first areas being provided with images thereon of micro-organisms susceptible to the microbiocidal composition, and the second of said isolated areas being composed of a material unaffected by cold water, each of these second areas being provided with images thereon of micro-organisms not susceptible to the microbiocidal composition, said first isolated areas being dissolvable upon contact with cold water while said second iso lated areas remain unaffected by contact with cold water, whereby when the instructional paper is entirely immersed in cold water, only said first areas are destroyed so as to provide an indication of the effectiveness of the microbiocidal composition.

2. The instructional paper of claim 1 in which said first isolated areas comprise a cold-water-soluble film coating on the surface of a base composed of a material unaffected by cold water.

3. The instructional paper of claim 2 in which said cold water soluble film is prepared from cold water soluble cellulose ethers. 

1. An instructional paper for demonstrating the effectiveness of a microbiocidal composition comprising a paper sheet having a plurality of first and second spaced isolated areas, the first of said isolated areas being composed of a cold-water-soluble material, each of these first areas being provided with images thereon of micro-organisms susceptible to the microbiocidal composition, and the second of said isolated areas being composed of a material unaffected by cold water, each of these second areas being provided with images thereon of micro-organisms not susceptible to tHe microbiocidal composition, said first isolated areas being dissolvable upon contact with cold water while said second isolated areas remain unaffected by contact with cold water, whereby when the instructional paper is entirely immersed in cold water, only said first areas are destroyed so as to provide an indication of the effectiveness of the microbiocidal composition.
 2. The instructional paper of claim 1 in which said first isolated areas comprise a cold-water-soluble film coating on the surface of a base composed of a material unaffected by cold water.
 3. The instructional paper of claim 2 in which said cold water soluble film is prepared from cold water soluble cellulose ethers. 